BACKGROUND: We evaluated the potential for QT/corrected QT (QTc) interval prolongation after sugammadex given with propofol or sevoflurane anaesthesia. METHODS: This was a two-factorial, randomized, parallel-group study in 132 healthy subjects. Anaesthesia was maintained with sevoflurane or propofol. At ~20 min following sevoflurane/propofol initiation, sugammadex 4 mg/kg or placebo was administered. Neuromuscular blocking agents were not administered. Electrocardiograms were recorded regularly. The primary variable was the time-matched mean difference in the Fridericia-corrected QT interval (QTcF) change from baseline for sugammadex versus placebo when combined with propofol or sevoflurane. No relevant QTcF prolongation was concluded if the upper one-sided 95 % confidence interval (CI) was below the 10 ms margin of regulatory non-inferiority, up to 30 min post-study drug. Blood samples were taken for pharmacokinetic analysis. An exploratory analysis evaluated potential QT/QTc effects of neostigmine 50 μg/kg/glycopyrrolate 10 μg/kg in combination with propofol. RESULTS: The estimated mean QTcF differences between sugammadex and placebo ranged from -2.4 to 0.6 ms when combined with either anaesthetic. The largest upper one-sided 95 % CI for the mean QTcF difference between sugammadex and placebo was 2 ms, occurring 2 min post-dosing. Propofol and sevoflurane resulted in mean QTcF increases exceeding 10 and 30 ms, respectively. On top of these prolongations, the effect of sugammadex was negligible at all timepoints. The mean peak sugammadex concentration was 66.5 μg/mL, with exposure similar in the sevoflurane/propofol groups. The mean QTcF changes from baseline following neostigmine/glycopyrrolate in 10 healthy subjects ranged between -1.4 and 3.6 ms. CONCLUSION:Sugammadex 4 mg/kg does not cause clinically relevant QTc interval prolongation versus placebo when combined with propofol or sevoflurane.
RCT Entities:
BACKGROUND: We evaluated the potential for QT/corrected QT (QTc) interval prolongation after sugammadex given with propofol or sevoflurane anaesthesia. METHODS: This was a two-factorial, randomized, parallel-group study in 132 healthy subjects. Anaesthesia was maintained with sevoflurane or propofol. At ~20 min following sevoflurane/propofol initiation, sugammadex 4 mg/kg or placebo was administered. Neuromuscular blocking agents were not administered. Electrocardiograms were recorded regularly. The primary variable was the time-matched mean difference in the Fridericia-corrected QT interval (QTcF) change from baseline for sugammadex versus placebo when combined with propofol or sevoflurane. No relevant QTcF prolongation was concluded if the upper one-sided 95 % confidence interval (CI) was below the 10 ms margin of regulatory non-inferiority, up to 30 min post-study drug. Blood samples were taken for pharmacokinetic analysis. An exploratory analysis evaluated potential QT/QTc effects of neostigmine 50 μg/kg/glycopyrrolate 10 μg/kg in combination with propofol. RESULTS: The estimated mean QTcF differences between sugammadex and placebo ranged from -2.4 to 0.6 ms when combined with either anaesthetic. The largest upper one-sided 95 % CI for the mean QTcF difference between sugammadex and placebo was 2 ms, occurring 2 min post-dosing. Propofol and sevoflurane resulted in mean QTcF increases exceeding 10 and 30 ms, respectively. On top of these prolongations, the effect of sugammadex was negligible at all timepoints. The mean peak sugammadex concentration was 66.5 μg/mL, with exposure similar in the sevoflurane/propofol groups. The mean QTcF changes from baseline following neostigmine/glycopyrrolate in 10 healthy subjects ranged between -1.4 and 3.6 ms. CONCLUSION:Sugammadex 4 mg/kg does not cause clinically relevant QTc interval prolongation versus placebo when combined with propofol or sevoflurane.
Authors: Anton Bom; Mark Bradley; Ken Cameron; John K Clark; Jan Van Egmond; Helen Feilden; Elizabeth J MacLean; Alan W Muir; Ronald Palin; David C Rees; Ming-Qiang Zhang Journal: Angew Chem Int Ed Engl Date: 2002-01-18 Impact factor: 15.336
Authors: Pieter-Jan de Kam; Jacqueline van Kuijk; Jean Smeets; Torben Thomsen; Pierre Peeters Journal: Int J Clin Pharmacol Ther Date: 2012-08 Impact factor: 1.366
Authors: Julia M Adam; D Jonathan Bennett; Anton Bom; John K Clark; Helen Feilden; Edward J Hutchinson; Ronald Palin; Alan Prosser; David C Rees; Georgina M Rosair; Donald Stevenson; Gary J Tarver; Ming-Qiang Zhang Journal: J Med Chem Date: 2002-04-25 Impact factor: 7.446
Authors: Karin S Khuenl-Brady; Magnus Wattwil; Bernard F Vanacker; José I Lora-Tamayo; Henk Rietbergen; José A Alvarez-Gómez Journal: Anesth Analg Date: 2009-08-27 Impact factor: 5.108